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Biomedical subjects

A Martin

Publications and source records attributed to A Martin.

At least 109 records · Page 6Linked to original sources
PubMed2001

Three membrane-proximal amino acids in the human parainfluenza type 2 (HPIV 2) F protein are critical for fusogenic activity.

In this study, we investigated the role of the membrane-proximal region of the human parainfluenza virus type 2 (HPIV2) F protein by mutational analysis, including deletion, insertion, and substitution. Deletion or replacement of the entire 12 amino acid region (aa 474-485) of the HPIV2 F protein completely abolished its fusion activity when coexpressed with the HPIV2 HN protein. Deletion of groups of four of aa 478-485, single alanine, or other amino acid substitutions among aa 478-485 had minimal or limited effects on HPIV2 F/HN-induced cell fusion. However, a significant reduction in, or complete inhibition of, fusion activity was observed when aa 474-477 were deleted, or the N475, F476, or F477 residues were singly substituted with alanine. In addition, insertions of four amino acids at this region or deletion of eight or more amino acids significantly reduced F protein fusion activity. The oligomerization patterns and levels of cell surface expression of the mutant F proteins were compared to those of the wild-type HPIV2 F protein. The mutant HPIV2 F proteins defective in fusion were also found to be unable to initiate hemifusion, indicating that there is a specific requirement for three specific amino acids as well as the spacing in this region for initiating lipid mixing.

Amino Acids↗
PubMed2001

Antiquity of the biological sulphur cycle: evidence from sulphur and carbon isotopes in 2700 million-year-old rocks of the Belingwe Belt, Zimbabwe.

Sulphur and carbon isotopic analyses on small samples of kerogens and sulphide minerals from biogenic and non-biogenic sediments of the 2.7 x 10(9) years(Ga)-old Belingwe Greenstone Belt (Zimbabwe) imply that a complex biological sulphur cycle was in operation. Sulphur isotopic compositions display a wider range of biological fractionation than hitherto reported from the Archaean. Carbon isotopic values in kerogen record fractionations characteristic of rubisco activity methanogenesis and methylotrophy and possibly anoxygenic photosynthesis. Carbon and sulphur isotopic fractionations have been interpreted in terms of metabolic processes in 2.7 Ga prokaryote mat communities, and indicate the operation of a diverse array of metabolic processes. The results are consistent with models of early molecular evolution derived from ribosomal RNA.

Archaea↗
PubMed2001

Pivotal phase III trial of two dose levels of denileukin diftitox for the treatment of cutaneous T-cell lymphoma.

PURPOSE: The objective of this phase III study was to determine the efficacy, safety, and pharmacokinetics of denileukin diftitox (DAB389IL-2, Ontak [Ligand Pharmaceuticals Inc, San Diego, CA]) in patients with stage Ib to IVa cutaneous T-cell lymphoma (CTCL) who have previously received other therapeutic interventions. PATIENTS AND METHODS: Patients with biopsy-proven CTCL that expressed CD25 on > or = 20% of lymphocytes were assigned to one of two dose levels (9 or 18 microg/kg/d) of denileukin diftitox administered 5 consecutive days every 3 weeks for up to 8 cycles. Patients were monitored for toxicity and clinical efficacy, the latter assessed by changes in disease burden and quality of life measurements. Antibody levels of antidenileukin diftitox and anti-interleukin-2 and serum concentrations of denileukin diftitox were also measured. RESULTS: Overall, 30% of the 71 patients with CTCL treated with denileukin diftitox had an objective response (20% partial response; 10% complete response). The response rate and duration of response based on the time of the first dose of study drug for all responders (median of 6.9 months with a range of 2.7 to more than 46.1 months) were not statistically different between the two doses. Adverse events consisted of flu-like symptoms (fever/chills, nausea/vomiting, and myalgias/arthralgias), acute infusion-related events (hypotension, dyspnea, chest pain, and back pain), and a vascular leak syndrome (hypotension, hypoalbuminemia, edema). In addition, 61% of the patients experienced transient elevations of hepatic transaminase levels with 17% grade 3 or 4. Hypoalbuminemia occurred in 79%, including 15% with grade 3 or 4 changes. Tolerability at 9 and 18 microg/kg/d was similar, and there was no evidence of cumulative toxicity. CONCLUSION: Denileukin diftitox has been shown to be a useful and important agent in the treatment of patients whose CTCL is persistent or recurrent despite other therapeutic interventions.

Adult↗
PubMed2001

Improving diagnostic yield in brain biopsy: coupling spectroscopic targeting with real-time needle placement.

The purpose of this study was to determine the utility of intraoperative magnetic resonance spectroscopy (MRS) for targeting during brain biopsy using a skull-mounted trajectory guide. From January 1999 to January 2001, 17 patients had intraoperative MRS-guided brain biopsy using a trajectory guide. Ten had turbo spectroscopic imaging (TSI), and seven had both SVS (single-voxel spectroscopy) and TSI. Prospective stereotaxy was used to align the device in a short-bore 1.5-T MR scanner. Areas of elevated choline relative to creatine on SVS and TSI were targeted during the biopsy. Intraoperative imaging confirmed appropriate positioning of the biopsy needle at the time of tissue sampling in all cases. All 17 biopsies (100%) yielded diagnostic tissue. Six patients (34%) had glioblastomas multiforme, three (18%) had anaplastic astrocytomas, three (18%) had anaplastic oligodendrogliomas, two (12%) had radiation necrosis, and one each (6%) had germinoma, ganglioglioma, and astrocytoma. Postoperative imaging confirmed the absence of clinically and radiographically relevant hemorrhage. The findings on SVS correlated with the pathology in all seven cases (100%). In 13 of 17 patients (76%) who had TSI, the spectra correlated well with the permanent pathologic examination. The SVS and TSI spectra were similar in six of seven (86%) cases. Intraoperative MRS-guided brain biopsy using a trajectory guide is a simple, safe, and accurate technique for accessing areas of the brain of diagnostic interest. J. Magn. Reson. Imaging 2001;13:12-15.

Biopsy, Needle↗
PubMed2001

Ability of the American College of Rheumatology 1987 criteria to predict rheumatoid arthritis in patients with early arthritis and classification of these patients two years later.

OBJECTIVE: To determine how well the American College of Rheumatology (ACR; formerly, the American Rheumatism Association) 1987 classification criteria for rheumatoid arthritis (RA), when used at study inclusion in a cohort of 270 patients with early (<1 year) arthritis, predicted a diagnosis of RA 2 years later and how well they classified these patients at the end of the 2 years. METHODS: Patients were evaluated during 1995-1997 at 7 hospitals in the Brittany region of France. Patients were evaluated at 6-month intervals until November 1999. The diagnosis made by a panel of 5 rheumatologists (P5R) after the last visit was used as the "gold standard." The ACR 1987 criteria for RA were applied prospectively, without taking into account the initial diagnosis. RESULTS: At the last visit (mean +/- SD followup 29.1 +/- 11.8 months; median 30 months), the P5R diagnosed RA in 98 patients. At the last visit, classification by the ACR criteria was satisfactory, and the combination of an office-based rheumatologist's (OBR's) diagnosis of RA and fulfillment of the ACR criteria was sensitive (87%; 85 of 98 RA patients had both) and highly specific (99%; 170 of 172 non-RA patients did not have both). Application of the criteria at the first visit was of limited value for predicting a diagnosis of RA 2 years later. CONCLUSION: After a 2-year followup, the ACR 1987 classification criteria used in combination with an OBR's diagnosis were effective in distinguishing patients with and without RA. The criteria were not useful for predicting RA in patients with arthritis onset within the previous year. Some patients who met the criteria at baseline and after 2 years did not have RA, suggesting that incorporating exclusion criteria may improve the performance of the ACR criteria when used without taking into account the diagnosis by a rheumatologist, particularly in early arthritis.

Adolescent↗
PubMed2001

Efficacy of once-daily tobramycin monotherapy for acute pulmonary exacerbations of cystic fibrosis: a preliminary study.

Our objective was to compare the efficacy, safety, and microbiology of once-daily intravenous (IV) tobramycin with conventional 8-hourly tobramycin/ceftazidime IV therapy for acute Pseudomonas aeruginosa (PA) pulmonary exacerbations in cystic fibrosis (CF). CF patients with PA-induced pulmonary exacerbations were allocated to receive either once-daily tobramycin (Mono) or conventional therapy with tobramycin/ceftazidime given 8-hourly (Conv). The two longitudinal groups received therapy in a double-blind, randomized manner over a period of 2 years. Tobramycin doses were adjusted to achieve a daily area under the time-concentration curve of 100 mg x hr/L in both groups. Results were assessed for both short-term changes (efficacy and safety after 10 days of IV antibiotics during acute exacerbations) and long-term changes (efficacy, safety, and sputum microbiology between study entry and exit). Pulmonary function tests (PFTs) on admission were similar in both groups. After 10 days of IV antibiotics, absolute mean improvements in percent of predicted PFTs were 12.8, 12.1, and 13.7 for forced expiratory volume in 1 sec (FEV(1)), forced vital capacity (FVC), and forced expired flow between 25--75% of FVC (FEF(25--75%)) in the Conv group (n = 51 admissions) compared to 10.6, 9.9, and 10.6 in the Mono group (n = 47)(P<0.05 for all). Sixteen percent in the Conv group and 15% of patients in the Mono group did not respond to therapy by day 10. Long-term PFT patterns were similar for the Conv and Mono groups. The time between admissions did not differ. The Mono group showed a significant increase in tobramycin minimum inhibitory concentrations (MICs) against PA from study entry to study exit (P = 0.02, n = 27 strains); this failed to reach significance in the Conv group (P = 0.08, n = 25). There was no significant increase in the number of isolates, with MIC> or =8 mg/L in both groups. No short- or long-term changes in audiology or serum creatinine were found in either group. After 10 days of IV therapy, the urinary enzyme N-acetyl-beta-d-glucosaminidase/creatinine ratios increased in both groups (P0.05). This increase was greater in the Conv compared to the Mono group (P < 0.05). We conclude that this pilot study indicates once-daily tobramycin therapy to be as effective and safe as conventional 8-hourly tobramycin/ceftazidime therapy. Combination antibacterial therapy appears to offer no clinical advantage over once-daily tobramycin monotherapy. Tobramycin once-daily monotherapy is a potential alternative to conventional IV antibacterial therapy which deserves further investigation, including the impact on susceptibility of PA to tobramycin.

Adolescent↗
PubMed2001

Structure and functional genomics of lipopolysaccharide expression in Haemophilus influenzae.

The involvement of genes in the lic loci in H. influenzae LPS expression has been known for some time. However, it was not until recently that it was shown that the lic1 locus contains genes required for phase variable expression of phosphocholine substituents, while genes in the lic2 locus and lgtC are required for expression of the globoside trisaccharide, alpha-D-Galp-(1 --> 4)-beta-D-Galp-(1 --> 4)-beta-D-Glcp (i.e., the pK blood group epitope). The availability of the complete sequence of the H. influenzae strain Rd genome has facilitated significant progress in understanding the role of these and other genes in the expression and biosynthesis of LPS. We have employed a comparative structural fingerprinting strategy to establish the structural relationships among LPS from H. influenzae mutant strains in which putative biosynthesis genes were inactivated. Using this functional genomics approach, we have gained considerable insight into the genetic basis for intra-strain and strain-to-strain variation in epitope expression.

Base Sequence↗
PubMed2001

Postal administration compared with nurse-supported administration of the QUALEFFO-41 in a population sample: comparison of results and assessment of psychometric properties.

The objective of this study was to test the psychometric properties of the QUALEFFO-41, an osteoporosis-specific health-related quality of life (HRQoL) measure, in a population sample. The study involved repeated administration of QUALEFFO-41 and another measure of HRQoL, the SF-36, to a stratified random population sample to test reliability and validity of instrument. The study was set in urban Harrow, Middlesex, UK and rural Cambridgeshire, UK. The participants were 83 males and 88 females aged 65-80+ years. Of the 230 individuals contacted 76.5% participated. The test-retest reliability of most QUALEFFO-41 items was good (Kappa 0.59-0.91) but two items had lower repeatability. Internal consistency was also generally good, but suggestive of some redundancy for three domains. The QUALEFFO-41 domains in general correlated well with SF-36 domains (r = 0.57 to r = 0.87), suggesting good validity. The QUALEFFO-41 has been shown to be a reliable and valid disease-specific HRQoL measure for osteoporosis. In population samples, it can be administered by post, or with a professional available to answer queries. Some specific items perform less well than may be desired and there is evidence of some redundancy, but further investigation is required and there are not yet grounds for textual change. We recommend continued use of this well-validated, reliable instrument.

Aged↗
PubMed2001

Predator-prey models with delay and prey harvesting.

It is known that predator-prey systems with constant rate harvesting exhibit very rich dynamics. On the other hand, incorporating time delays into predator-prey models could induce instability and bifurcation. In this paper we are interested in studying the combined effects of the harvesting rate and the time delay on the dynamics of the generalized Gause-type predator-prey models and the Wangersky-Cunningham model. It is shown that in these models the time delay can cause a stable equilibrium to become unstable and even a switching of stabilities, while the harvesting rate has a stabilizing effect on the equilibrium if it is under the critical harvesting level. In particular, one of these models loses stability when the delay varies and then regains its stability when the harvesting rate is increased. Computer simulations are carried to explain the mathematical conclusions.

Animals↗
PubMed2001

Time of day effects on isometric and isokinetic torque developed during elbow flexion in humans.

The aim of this study was, firstly, to confirm or refute the existence of circadian rhythms during several velocities of concentric action of the elbow flexor muscles and, secondly, to compare the characteristics of these circadian rhythms with those obtained during isometric actions. Eight volunteer subjects participated in this study. The circadian rhythms were obtained from six test sessions (TS) carried out at different times of day over 6 days with only one TS a day. During each TS, oral temperature and the torque of the muscle action were measured. The subjects made, on an isokinetic ergometer, two maximal isokinetic concentric elbow flexions at five angular velocities (60, 120, 180, 240 and 300 degrees.s-1) and at an angle of 60 degrees. Torque-angular velocity relationships, which characterised the functioning of the muscle during concentric and isometric actions, were established for the different times of day. The values of the torque recorded at each of the angular velocities presented a clear circadian rhythm. After normalisation of the torque values, no significant differences were observed among the computed characteristics of the circadian rhythms obtained at different angular velocities. Since the circadian rhythms during isometric and concentric torque were the same, the characteristics of the circadian rhythms of the musculo-skeletal system can be studied using either type of muscle action. The results indicated that torque and temperature varied concomitantly during the day. Thus, the recording of body temperature allows one to estimate the times of occurrence of maximal and minimal values in the circadian rhythm of muscle torque.

Adult↗
PubMed2001

KCNQ1/KCNE1 potassium channels in mammalian vestibular dark cells.

The high [K(+)] in the inner ear endolymph is essential for mechanosensory transduction in hearing and balance. Several ion channels, including a slowly activating, voltage-dependent, outwardly conducting K(+) channel composed of the KCNQ1 (KvLQT1) and KCNE1 (IsK/minK) subunits, are expressed at the apical surface of vestibular dark cells. We investigated the underlying molecular mechanisms of this conductance using in situ hybridization, RT-PCR, and immunocytochemistry and by tracking the ultrastructural changes of vestibular structures in kcne1(-/-) mice. In the wild type mice, the KCNE1 and KCNQ1 proteins are expressed specifically at the apical membrane of dark cells, as early as gestational day (GD) 17 for KCNE1 while KCNQ1 mRNAs can be detected at GD 18. This is the first demonstration that the two protein components of this potassium channel co-localize in a polarized fashion at the cellular level. Although the vestibular end-organs are normal at birth in kcne1(-/-) mice, they begin to show modifications during postnatal development: we observed an increase in the height of the dark cells, in their number of mitochondria, and in basolateral membrane infoldings. Subsequently, the epithelium degenerates and the endolymphatic space collapses. Similar changes are known to occur in the cardio-auditory Jervell--Lange-Nielsen syndrome which is caused by mutations in the same channel.

Amino Acid Sequence↗
PubMed2001

Is resistant hypertension really resistant?

BACKGROUND: Managing resistant hypertension is difficult and mostly involves expensive testing seeking an underlying secondary cause. This study was undertaken to determine 1) the extent of the white-coat phenomenon in patients with resistant hypertension, and 2) whether 24-h ambulatory blood pressure (BP) monitoring (ABPM) or having BP recorded by a nurse instead of the referring doctor could clarify how many apparently resistant hypertensives actually have controlled BP. METHODS: This study involved 611 patients with BP > or = 140/90 mm Hg who were referred for 24-h ABPM by their specialist or general practitioner, including 277 patients who were taking no antihypertensives (group 1), 216 taking one or two antihypertensive drugs (group 2), and 118 taking at least three antihypertensives in combination (group 3). Each had BP recorded by one of two nurses before 24-h ABPM. Controlled BP was defined as awake ambulatory BP <135/85 mm Hg and the white-coat effect was the difference between the BP recorded by the referring doctor or nurse and the average awake ambulatory BP. RESULTS: Those with resistant hypertension (group 3) were older (61 years (12) v group 1: 46 years (14) and group 2: 56 (14) years; P < .001), but were of similar weight, height, and arm circumference to the other groups. Referral systolic, but not diastolic BP was higher in resistant hypertensives (mean 171/95 v 154/95 mm Hg and 164/94 mm Hg, respectively, P < .001 for systolic BP only). Twenty-eight percent of resistant hypertensives and 32% of those taking no antihypertensive drugs had normal awake ambulatory BP and the white-coat effect attributable to the referring doctor was always greater than that due to the nurse (range 16 to 26/12 to 14 mm Hg v 9 to 17/4 mm Hg, P < .001). Nurse recorded BP was highly sensitive (97%) in identifying awake hypertension but lacked specificity (57%) to replace ABPM. CONCLUSION: Our results show that approximately one in four patients with apparent resistant hypertension referred for ABPM have controlled BP and one-third of patients referred for initial evaluation of office or clinic hypertension have normal BP using ABPM, ie, white-coat hypertension. Twenty-four-hour ABPM appears an appropriate initial step before further investigating or treating patients with apparently resistant hypertension.

Adult↗
PubMed2001

Breast adenocarcinoma complicating Kallmann's syndrome.

Carcinoma of the breast is relatively rare among men, accounting for less than 1% of all malignancies. An increased risk has been associated with benign breast diseases, such as gynecomastia, Klinefelter's syndrome, testicular disorders, exogenous estrogen use, radiation, or a family history of male or female breast cancer. To date, hypogonadotrophic hypogonadism has never been associated with male breast cancer. We report here the first case of breast cancer coexisting with Kallmann's syndrome in a 66-year-old man.

Journal Article↗
PubMed2001

Semantic memory and the brain: structure and processes.

Recent functional brain imaging studies suggest that object concepts may be represented, in part, by distributed networks of discrete cortical regions that parallel the organization of sensory and motor systems. In addition, different regions of the left lateral prefrontal cortex, and perhaps anterior temporal cortex, may have distinct roles in retrieving, maintaining and selecting semantic information.

Animals↗
PubMed2001

Abnormally increased semantic priming in children with symptomatic HIV-1 disease: evidence for impaired development of semantics?

Language deficits are a major characteristic of neurobehavioral dysfunction in pediatric HIV disease. An object decision task, which assessed reaction time facilitation following a semantic or identical prime in comparison to an unrelated prime, was used to investigate whether semantic processing abnormalities could be responsible, in part, for these deficits. Thirty children with vertically acquired HIV infection (M age 9.0 years; range 6-13) participated. Either a picture of the same object (repetition prime), a semantically related object (semantic prime), a semantically unrelated object, or a nonsense object preceded a target picture, which in 50% of the cases was a real object. Brain scans of children were rated and used together with neurobehavioral functioning to classify children as having HIV-related CNS abnormalities (n = 13) or not (n = 17). Increased semantic priming but not repetition priming was associated with a greater degree of cortical atrophy. Furthermore, CNS compromised children had significantly faster reaction times following a semantic prime compared to an unrelated prime than non-compromised patients. This facilitation following semantic priming for the CNS compromised patients (13.3%) almost equaled the facilitation following repetition priming (15.3%) while for the non-compromised patients facilitation following semantic priming (7.9%) was clearly smaller than following repetition priming (14.6%). These data suggest that HIV infection in children may result in a reduced neural network leading to impoverished semantic representations characterized by poor differentiation between closely related objects.

Acquired Immunodeficiency Syndrome↗
PubMed2001

The phylogenetic placement of chondrichthyes: inferences from analysis of multiple genes and implications for comparative studies.

Elasmobranch fishes (sharks and rays) have proven valuable for inferring general and specific properties of molecular evolution through comparative studies with crown group vertebrates because they are the most ancient group of gnathostomes. Recent studies have questioned the conventional phylogenetic placement of sharks in the vertebrate tree, however. In this paper I review the importance of the basal position of Chondrichthyes for comparative biology and compile evidence from multiple, independent genes to evaluate the phylogenetic placement of sharks. The results suggests that alternative phylogenetic hypotheses of the relationships among the Chondrichthyes, Actinopterygii and Sarcopterygii can not be refuted with available data, implying that the assumption of the basal placement of sharks in the vertebrate tree is suspect. Resolving the phylogeny of basal vertebrates is important for testing hypotheses about the evolution of vertebrates, and the current lack of a robust phylogeny limits evolutionary inferences that can be gained from comparative studies that include sharks and rays.

Animals↗
PubMed2001

Renin angiotensin system gene polymorphisms in pediatric renal transplant recipients.

Genetic variability in the renin angiotensin system may modify renal responses to injury and disease progression. We therefore examined whether the insertion/deletion polymorphism of the angiotensin-converting enzyme (ACE) gene, the Met235-->Thr polymorphism of the angiotensinogen (AGT) gene, and the A1166-->C polymorphism of the angiotensin II type 1 receptor gene (ATR1) were associated with disease progression and outcome after renal transplantation (Tx) in 100 Caucasian pediatric renal transplant recipients. The observed allele frequencies were: DD 31%, DI 41% and II 28%, for ACE; MM 42%, MT 37% and TT 21%, for the methionine (Met)235-->threonine (Thr) polymorphism of AGT; and AA 51%, AC 38% and CC 11%, for the adenine (A)1166-->cytosine (C) gene polymorphism. The slope of 1/creatinine was determined by linear regression analysis of a median of 12 points before and after renal Tx, and the population was divided in two equal groups, according to the slope, both before and after Tx. There were no statistically significant differences for AGT, ACE, and ATR1 polymorphisms with regard to the slope of 1/creatinine before renal Tx. After renal Tx, the ACE II genotype (p = 0.024, chi-square test) and the presence of the I allele (p=0.033, chi-square test) were associated with a favorable slope of 1/creatinine. There was no association of the AGT or the ATR1 polymorphism with outcome after renal Tx, and none of the genotypes were associated with hypertension before or after renal Tx. We suggest that the beneficial association of disease progression after renal Tx with the II genotype and/or the presence of the I allele in our pediatric cohort might be explained by a lower activity of the circulating ACE enzyme associated with the I allele.

Adolescent↗